Infections due to group B streptococci (GBS) are the most common single cause of sepsis and meningitis in newborns in developed countries (3, 31). Recent reports from some centers in the United States reflect a lower mortality (9 to 13%) than in series from the 1970s, perhaps as a result of earlier diagnosis and intensive care (1, 10). Nonetheless, fatal infections still occur, and equally important, up to 50% of survivors of GBS meningitis have chronic neurologic injury ranging from deafness and mild learning disabilities to profound motor, sensory, and cognitive impairment (3). Prevention rather than improved diagnosis or therapy is likely to have the most significant impact in further reducing GBS-related morbidity and mortality.
Because GBS capsular polysaccharide-specific antibodies appear to protect both experimental animals (23, 24) and human infants (4, 5) from GBS infection, some of the polysaccharides have been purified and tested in healthy adults as experimental vaccines (6). Were a safe and efficacious GBS vaccine available, it could be administered to women before or during pregnancy to elicit antibodies that would transfer to the fetus in utero and provide protection against neonatal infection. Of the three GBS polysaccharides (types Ia, II, and III) tested in volunteers, type II had the highest rate of immunogenicity, eliciting a type II-specific antibody response in 88% of previously nonimmune recipients (6). Although a variety of GBS serotypes have previously been recognized as contributing significantly to the percent of patients with GBS infection, type V has not been considered to be responsible for a significant percent of GBS infection. In neonates, the level of specific antibody required for protection against type II GBS infection is not precisely defined but has been estimated at 2 or 3 .mu.g/ml (6). In a vaccine recipient who achieves an antibody response only slightly above the minimum required for protection, the amount of maternal antibody transferred across the placenta may be inadequate to protect a premature infant, because of the incomplete transfer to the fetus of material immunoglobulin G (IgG), or an infant with late-onset infection, since the half-life of maternal IgG antibodies in the newborn is about 25 days (13). Many of the infants in these two groups of patients might be protected if the magnitude of the specific antibody response to vaccination were higher. The transfer of maternal IgG to the fetus increases throughout the third trimester, so a higher maternal antibody level would provide protection earlier, i.e., to a more premature infant (16). Similarly, higher maternal levels would result in longer persistence of maternal antibodies in the infant, thereby providing protection against late-onset disease, as well.
The immunogenicity of several bacterial polysaccharide antigens has been increased by the attachment of suitable carrier proteins to polysaccharides or to derivative oligosaccharides (2, 14, 17-19, 22, 27, 29, 30, 34). Desirable properties of polysaccharide-protein conjugate vaccines include enhanced immunogenicity of the polysaccharide, augmented hapten-specific antibody response to booster doses, and a predominance of IgG class antibodies. Recently, we have been successful in developing a GBS III-Tetanus Toxoid (TT) vaccine by using the side chain sialic acid moieties as sites of directed protein coupling (33). The III-TT vaccine elicited GBS type III-specific, opsonically active antibodies, while the unconjugated type III polysaccharide was nonimmunogenic in rabbits (33).